A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma (CheckMate 9DW)

A Randomized, Multi-center, Phase 3 Study of Nivolumab in Combination With Ipilimumab Compared to Sorafenib or Lenvatinib as First-Line Treatment in Participants With Advanced Hepatocellular Carcinoma

The main purpose of this study is to compare the overall survival (OS) of nivolumab plus ipilimumab versus standard of care (SOC) (sorafenib or lenvatinib) in all randomized participants with advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Ipilimumab; Drug: Sorafenib; Drug: lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 732
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Local Institution - 0136
  • San Miguel de Tucumán, Argentina, 4000
    • Local Institution - 0058
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1090AAS
      • Local Institution - 0037
    • Pilar, Buenos Aires, Argentina, B1629ODT
      • Local Institution - 0194
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Local Institution - 0282
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Local Institution - 0003
    • Liverpool, New South Wales, Australia, 1871
      • Local Institution - 0038
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0002
  • Queensland
    • Birtinya, Queensland, Australia, 4560
      • Local Institution - 0004
    • Herston, Queensland, Australia, 4029
      • Local Institution - 0013
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution - 0009
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0019
    • Fitzroy, Victoria, Australia, 3065
      • Local Institution - 0026
    • Melbourne, Victoria, Australia, 3004
      • Local Institution - 0001
    • St Albans, Victoria, Australia, 3021
      • Local Institution - 0020
• Austria
  • Graz, Austria, 8036
    • Local Institution - 0188
  • Klagenfurt, Austria, 9020
    • Local Institution - 0065
  • Vienna, Austria, 1090
    • Local Institution - 0186
  • Lower Austria
    • Sankt Pölten, Lower Austria, Austria, 3100
      • Local Institution - 0114
    • Wiener Neustadt, Lower Austria, Austria, 2700
      • Local Institution - 0057
• Belgium
  • Brussels, Belgium, 1070
    • Local Institution - 0034
  • Federal District, Belgium, 72115700
    • Local Institution - 0008
  • Ghent, Belgium, 9000
    • Local Institution - 0124
  • Ghent, Belgium, 9000
    • Local Institution - 0298
  • Haine-Saint-Paul, Belgium, 7100
    • Local Institution - 0099
  • Leuven, Belgium, 3000
    • Local Institution - 0064
  • Liège, Belgium, 4000
    • Local Institution - 0104
• Brazil
  • Paranã, Brazil, 81520-060
    • Local Institution - 0016
  • Rio de Janeiro, Brazil, 22793-080
    • Local Institution - 0015
  • São Paulo, Brazil, 01246-000
    • Local Institution - 0023
  • São Paulo, Brazil, 01323-900
    • Local Institution - 0022
  • São Paulo, Brazil, 04038-034
    • Local Institution - 0050
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055-450
      • Local Institution - 0278
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253190
      • Local Institution
    • Salvador, Estado de Bahia, Brazil, 41950-640
      • Local Institution - 0061
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Local Institution - 0181
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Local Institution - 0279
    • Pelotas, Rio Grande do Sul, Brazil, 96020-360
      • Local Institution - 0060
  • São Paulo
    • Jaú, São Paulo, Brazil, 17210-120
      • Local Institution - 0054
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0192
• Chile
  • Coquimbo Region
    • La Serena, Coquimbo Region, Chile, 1720430
      • Local Institution - 0094
  • RM
    • Santiago, RM, Chile, 7630372
      • Local Institution - 0283
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2520598
      • Local Institution - 0012
    • Viña del Mar, Región de Valparaíso, Chile, 2540402
      • Local Institution - 0216
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4780000
      • Local Institution - 0296
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile
      • Local Institution - 0095
    • Santiago, Santiago Metropolitan, Chile, 7710007
      • Local Institution - 0024
    • Santiago, Santiago Metropolitan, Chile, 8380456
      • Local Institution - 0156
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • Local Institution - 0146
    • Hefei, Anhui, China, 230022
      • Local Institution - 0120
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Local Institution - 0175
    • Beijing, Beijing Municipality, China, 100142
      • Local Institution - 0152
  • Fujian
    • Fuzhou, Fujian, China, 350002
      • Local Institution - 0151
    • Fuzhou, Fujian, China, 350014
      • Local Institution - 0121
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Local Institution - 0125
    • Guangzhou, Guangdong, China, 510515
      • Local Institution - 0150
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Local Institution - 0135
  • Hunan
    • Changsha, Hunan, China, 410011
      • Local Institution - 0059
    • Changsha, Hunan, China, 410006
      • Local Institution - 0109
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Local Institution - 0130
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Local Institution - 0145
    • Nanchang, Jiangxi, China, 330019
      • Local Institution - 0149
  • Jilin
    • Changchun, Jilin, China, 130021
      • Local Institution - 0162
    • Changchun, Jilin, China, 130102
      • Local Institution - 0166
  • Liaoning
    • Dalian, Liaoning, China, 116023
      • Local Institution - 0131
    • Shenyang, Liaoning, China, 110004
      • Local Institution - 0123
    • Shenyang, Liaoning, China, 110117
      • Local Institution - 0132
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Local Institution - 0133
  • Shan3xi
    • Xi'an, Shan3xi, China, 710100
      • Local Institution - 0307
    • Xi'an, Shan3xi, China, 710061
      • Local Institution - 0147
  • Shandong
    • Qingdao, Shandong, China, 266000
      • Local Institution - 0153
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Local Institution - 0134
  • Sichuan
    • Chongqing, Sichuan, China, 400030
      • Local Institution - 0179
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Local Institution - 0107
    • Hangzhou, Zhejiang, China, 310000
      • Local Institution - 0108
• Czechia
  • Brno, Czechia, 60200
    • Local Institution
  • Prague
    • Prague, Prague, Czechia, 14059
      • Local Institution - 0274
• France
  • Amiens, France, 80054
    • Local Institution - 0068
  • Caen, France, 14033
    • Local Institution - 0116
  • Clichy, France, 92110
    • Local Institution - 0069
  • Dijon, France, 21000
    • Local Institution - 0138
  • Grenoble, France, 38043
    • Local Institution - 0081
  • Lyon, France, 69004
    • Local Institution - 0070
  • Marseille, France, 13009
    • Local Institution
  • Montpellier, France, 34295
    • Local Institution - 0082
  • Nice, France, 6202
    • Local Institution - 0067
  • Pessac, France, 33604
    • Local Institution - 0025
  • Poitiers, France, 86021
    • Local Institution - 0137
  • Toulouse, France, 31059
    • Local Institution - 0042
  • Vandœuvre-lès-Nancy, France, 54500
    • Local Institution - 0071
  • Villejuif, France, 94800
    • Local Institution - 0051
• Germany
  • Bonn, Germany, 53127
    • Local Institution - 0231
  • Cologne, Germany, 50937
    • Local Institution - 0028
  • Essen, Germany, 45147
    • Local Institution - 0052
  • Freiburg im Breisgau, Germany, 79106
    • Local Institution - 0185
  • Hamburg, Germany, 20246
    • Local Institution - 0006
  • Hanover, Germany, 30625
    • Local Institution - 0102
  • Leipzig, Germany, 04103
    • Local Institution - 0118
  • Mainz, Germany, 55131
    • Local Institution - 0031
  • Mannheim, Germany, 68167
    • Local Institution - 0056
  • München, Germany, 81675
    • Local Institution
  • North Rhine-Westphalia, Germany, 45136
    • Local Institution - 0053
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Local Institution - 0005
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Local Institution - 0036
  • Hong Kong, Hong Kong
    • Local Institution - 0032
• Italy
  • Candiolo, Italy, 10060
    • Local Institution - 0084
  • Milan, Italy, 20122
    • Local Institution - 0039
  • Novara, Italy, 28100
    • Local Institution - 0100
  • Padova, Italy, 35128
    • Local Institution - 0219
  • Parma, Italy, 43126
    • Local Institution - 0033
  • Roma, Italy, 00128
    • Local Institution - 0112
  • Rome, Italy, 00168
    • Local Institution - 0079
  • Siena, Italy, 53100
    • Local Institution - 0111
  • Vicenza, Italy, 36100
    • Local Institution - 0044
  • Forli-Cesena
    • Meldola, Forli-Cesena, Italy, 47014
      • Local Institution - 0110
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Local Institution - 0101
• Japan
  • Chiba, Japan, 260-8677
    • Local Institution - 0204
  • Fukuoka, Japan, 830-0011
    • Local Institution - 0178
  • Hiroshima, Japan, 7348551
    • Local Institution - 0177
  • Sapporo, Japan, 0600033
    • Local Institution - 0155
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 2778577
      • Local Institution - 0193
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0024
      • Local Institution - 0203
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Local Institution - 0176
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Local Institution - 0262
    • Yokohama, Kanagawa, Japan, 2320024
      • Local Institution - 0200
  • Kyoto
    • Kyoto, Kyoto, Japan, 602-8566
      • Local Institution - 0189
  • Nara
    • Kashihara, Nara, Japan, 634-8522
      • Local Institution - 0261
  • Osaka
    • Abeno-ku, Osaka, Japan, 5458586
      • Local Institution - 0263
    • Sayama, Osaka, Japan, 5898511
      • Local Institution - 0127
  • Saga-ken
    • Saga, Saga-ken, Japan, 8408571
      • Local Institution - 0281
  • Saitama
    • Iruma-gun, Saitama, Japan, 3500495
      • Local Institution - 0258
  • Shizuoka
    • Izunokuni-shi, Shizuoka, Japan, 410-2295
      • Local Institution - 0259
  • Tokyo
    • Minato, Tokyo, Japan, 105-8470
      • Local Institution - 0128
    • Minato-ku, Tokyo, Japan, 105-8470
      • Local Institution - 0122
    • Mitaka, Tokyo, Japan, 181-8611
      • Local Institution - 0201
    • Musashino-shi, Tokyo, Japan, 180-8610
      • Local Institution - 0199
• New Zealand
  • Auckland, New Zealand, 1023
    • Local Institution - 0047
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Local Institution - 0286
• Poland
  • Gdansk, Poland, 80219
    • Local Institution - 0148
  • Otwock, Poland, 05-400
    • Local Institution - 0049
  • Warsaw, Poland, 02-034
    • Local Institution - 0092
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Local Institution - 0289
  • San Juan, Puerto Rico, 00927-4308
    • Local Institution - 0035
• Romania
  • Bucharest, Romania, 022328
    • Local Institution - 0164
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0165
  • Craiova, Romania, 200385
    • Local Institution
  • Timișoara, Romania, 300166
    • Local Institution - 0163
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Local Institution - 0103
• Russia
  • Arkhangelsk, Russia, 163045
    • Local Institution - 0029
  • Barnaul, Russia, 656045
    • Local Institution - 0066
  • Chelyabinsk, Russia, 454087
    • Local Institution - 0074
  • Moscow, Russia, 115478
    • Local Institution - 0007
  • Pyatigorsk, Russia, 357502
    • Local Institution - 0072
  • Saint Petersburg, Russia, 197758
    • Local Institution - 0075
  • Saint Petersburg, Russia, 198255
    • Local Institution - 0091
  • Sochi, Russia, 354057
    • Local Institution - 0073
• Singapore
  • Singapore, Singapore, 258499
    • Local Institution - 0017
  • Singapore, Singapore, 308442
    • Local Institution - 0174
  • Singapore, Singapore, 168583
    • Local Institution - 0048
• South Korea
  • Busan, South Korea, 49241
    • Local Institution - 0142
  • Gyeonggi-do, South Korea, 010408
    • Local Institution - 0097
  • Gyeongsangnam-do, South Korea, 050612
    • Local Institution - 0098
  • Seoul, South Korea, 03722
    • Local Institution - 0141
  • Seoul, South Korea, 05505
    • Local Institution - 0140
  • Seoul, South Korea, 06351
    • Local Institution - 0139
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13496
      • Local Institution - 0143
  • Seoul
    • Guro-gu, Seoul, South Korea, 8308
      • Local Institution - 0167
    • Jongno-gu, Seoul, South Korea, 03080
      • Local Institution - 0062
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0297
  • Barcelona, Spain, 08036
    • Local Institution - 0055
  • Barcelona, Spain, 08908
    • Local Institution - 0089
  • Córdoba, Spain, 14004
    • Local Institution - 0090
  • El Palmar, Spain, 30120
    • Local Institution - 0087
  • Madrid, Spain, 28007
    • Local Institution - 0041
  • Madrid, Spain, 28028
    • Local Institution - 0093
  • Madrid, Spain, 28035
    • Local Institution - 0290
  • Majadahonda, Spain, 28222
    • Local Institution - 0045
  • Pamplona, Spain, 31008
    • Local Institution - 0085
  • Santander, Spain, 39008
    • Local Institution - 0088
  • Zaragoza, Spain, 50009
    • Local Institution - 0040
• Switzerland
  • Bern, Switzerland, 3010
    • Local Institution - 0063
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Local Institution - 0272
  • Kaohsiung City, Taiwan, 83301
    • Local Institution - 0096
  • Taichung, Taiwan, 40447
    • Local Institution - 0105
  • Taichung, Taiwan, 40705
    • Local Institution - 0271
  • Tainan, Taiwan, 704
    • Local Institution - 0168
  • Tainan, Taiwan, 736
    • Local Institution - 0270
  • Taipei, Taiwan, 10002
    • Local Institution - 0144
  • Taipei, Taiwan, 11266
    • Local Institution - 0078
  • Taoyuan District, Taiwan, 333
    • Local Institution - 0173
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Local Institution - 0160
  • London, United Kingdom, SE5 9RS
    • Local Institution - 0129
  • Greater London
    • London, Greater London, United Kingdom, W12 OHS
      • Local Institution - 0171
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Local Institution - 0154
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Local Institution - 0292
  • California
    • Coronado, California, United States, 92118
      • Local Institution - 0288
    • Duarte, California, United States, 91010-3012
      • Local Institution - 0157
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Local Institution - 0077
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Local Institution - 0027
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0190
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Local Institution
    • Detroit, Michigan, United States, 48202
      • Local Institution - 0018
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Local Institution - 0295
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Local Institution - 0043
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Local Institution - 0284
  • Texas
    • Dallas, Texas, United States, 75203
      • Local Institution - 0304
    • Houston, Texas, United States, 77030
      • Local Institution - 0202
    • Lubbock, Texas, United States, 79410
      • Local Institution - 0046
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Local Institution - 0172

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have a diagnosis of HCC based on histological confirmation
• Participants must have an advanced HCC
• Participants must have at least one Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable previously untreated lesion
• Child-Pugh score 5 or 6
• Eastern Cooperative Oncology Group (ECOG) performance status(PS) 0 or 1

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Prior liver transplant
• Episodes of hepatic encephalopathy (greater than or equal to [>=] Grade 2) within 12 months prior to randomization
• Active brain metastases or leptomeningeal metastases

Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + Ipilimumab	Drug: Nivolumab; Participants will receive nivolumab as intravenous (IV) infusion.; Drug: Ipilimumab; Participants will receive ipilimumab as IV infusion.
Active Comparator: Sorafenib/lenvatinib	Drug: Sorafenib; Participants will receive sorafenib as oral tablets.; Drug: lenvatinib; Participants will receive lenvatinib as oral capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	Up to 4 years
Objective Response Rate (ORR)	Up to 4 years
Time to Symptom Deterioration (TTSD)	Up to 4 years

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Yau T, Galle PR, Decaens T, Sangro B, Qin S, da Fonseca LG, Karachiwala H, Blanc JF, Park JW, Gane E, Pinter M, Pena AM, Ikeda M, Tai D, Santoro A, Pizarro G, Chiu CF, Schenker M, He A, Chon HJ, Wojcik-Tomaszewska J, Verset G, Wang QQ, Stromko C, Neely J, Singh P, Jimenez Exposito MJ, Kudo M; CheckMate 9DW investigators. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025 May 24;405(10492):1851-1864. doi: 10.1016/S0140-6736(25)00403-9. Epub 2025 May 8.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Estimated): July 9, 2026
• Study Completion (Estimated): July 9, 2026

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Benzene Derivatives; Urea; Acids, Heterocyclic; Phenylurea Compounds; Niacinamide; Nicotinic Acids; Sorafenib; Nivolumab; Ipilimumab; lenvatinib
• Other Study ID Numbers: CA209-9DW

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No